ARTEMIS-001: Phase 1 study of HS-20093, a B7-H3–targeting antibody-drug conjugate, in patients with advanced solid tumor.
Authors: Jie Wang, Jianchun Duan, Ligang Xing, Yuping Sun, Wei Guo, Haiying Wang, Jianhua Chen, Liang Han, Baogang Liu, Qiming Wang, Ying Hu, Hongying Wei, Chuan Li, Qiqi Huang, Yiwei Dong, Qiong Wu
Journal: Journal of Clinical Oncology (2023)

3017 Background: B7-H3, a member of the B7 superfamily, is highly expressed in various solid tumors, but has limited expression at low level in normal tissues. HS-20093 is a B7-H3-targeted antibody-drug conjugate. It could be an attractive therapeutic option for advanced solid tumors, especially the patients (pts) who have failed in multi-line therapy requiring novel and more effective treatment. Methods: This is a first-in-human, multicenter, open-label phase 1 study of HS-20093 in advanced solid tumors (NCT05276609). Dose escalation part assessed safety and tolerability of intravenous HS-20093 with doses ranging from 1.0 to 16.0 mg/kg. The dose escalation schedule utilized an accelerated titration and interval 3+3 design. Pts with advanced solid tumor were required to have received prior standard therapy. HS-20093 is administrated intravenously every 3 weeks. Results: The study completed all planned dose cohorts (1.0 to 16.0 mg/kg) as of cutoff date (20 December 2022). In dose escalation study, 53 pts of multiple tumor types were enrolled and received ≥1 dose of HS-20093, which included 29 pts with non-small cell lung cancer, 11 pts with small cell lung cancer (SCLC), 9 pts with sarcoma and 4 pts with other advanced solid tumors. At baseline, 25 pts (47.2%) had received ≥3 prior lines therapy with a mean of 3.2 (range, 1-12) prior lines of therapy. Three pts experienced dose-limiting toxicities (1 pt at 12.0 mg/kg; 2 pts at 16.0 mg/kg). The maximum tolerated dose was determined to be 12.0 mg/kg. Treatment-emerged adverse events (TEAEs) occurred in 53 pts (100%). The most common TEAEs overall in ≥30% of pts were leukopenia, neutropenia, anemia, pyrexia, nausea, thrombocytopenia, hypoalbuminemia, vomiting, lymphopenia, infusion-related reaction and fatigue. No interstitial lung disease was reported. Of 40 response-evaluable pts, regardless of baseline B7-H3 expression level, 14 partial responses (PRs) were observed in pts treated with HS-20093 from 4.0 mg/kg to 12.0 mg/kg doses (response rate: 35.0%), including 9 confirmed PRs and 5 PRs awaiting confirmation. The disease control rate was 85.0% (34/40, 95% CI: 70.2-94.3). The patient with the longest treatment duration (349 days) remains on treatment. In the subset of 9 SCLC pts, 7 PRs were observed (response rate: 77.8%) with the median depth of response of 50.5%, including 3 confirmed PRs and 4 PRs awaiting confirmation. All responses of SCLC pts occurred at the first disease assessment; the median time to first response was 6 weeks. HS-20093 displayed anti-tumor activity in SCLC pts who have progressed on prior derivative of camptothecin treatment. Conclusions: The safety profile of HS-20093 was acceptable. HS-20093 demonstrated promising antitumor activity in several tumor types, especially in SCLC. The further dose expansion study on efficacy and safety of HS-20093 in selected tumor types is ongoing. Clinical trial information: NCT05276609 .